Dr. Raul Chavez-Valdez is an assistant professor in the Department of Pediatrics with great interest in the mechanisms of delayed injury and repair/regeneration in the developing neonatal brain following injury, specifically following hypoxic-ischemic encephalopathy (birth asphyxia). He collaborates with Dr. Frances Northington (Pediatrics) and Dr. Lee Martin (Pathology/Neuroscience) in unveiling the importance of programmed necrosis in the setting of brain injury induced by birth asphyxia. He is especially interested in the role of brain derived neurotrophic factor and neurotrophin-4 following birth asphyxia and the changes that may explain the suspected excitatory/ inhibitory (E/I) imbalance particularly in the hippocampus. His work is highly translational since delayed hippocampal injury due to E/I imbalance may explain memory deficits observed despite therapeutic hypothermia in neonates suffering birth asphyxia. All of these aspects of developmental neuroplasticity are the base of his Career Development Award (NIH/NINDS-K08 award) and applications to other agencies. Additionally, he is part of multiple clinical efforts as part of the Neuroscience Intensive Care Nursery (NICN). He has been a Sutland-Pakula Endowed Fellow of Neonatal Research since September 2013.

Our research aims to expand the understanding of how hormones regulate pancreatic islets in health and disease. Currently, a major focus of the lab is to define the normal adaptations of islets, particularly insulin-producing beta-cells, to the metabolic stress of pregnancy, and to determine how defective adaptation contributes to gestational diabetes mellitus (GDM). We anticipate that elucidating physiologic mechanisms of gestational beta-cell adaptation will identify novel therapeutic strategies to expand functional beta-cell mass which would help in the treatment of all types of diabetes.

Research in the Rosalyn Stewart Lab focuses on medical education and curriculum development; ambulatory medicine; community outreach and advocacy; health outcomes; and preventive medicine. Topics of published studies include the administration of vaccinations, care quality of pediatric sickle-cell disease patients and the improvement of transitional care to reduce hospital readmission rates.

The Radiopharmaceutical Therapy and Dosimetry (RTD) Lab has two missions: 1. Support clinical Radiopharmaceutical Therapy (RPT) trials by performing patient-specific dosimetry and developing novel methods that advance this field and illustrate the impact of a precision medicine approach to implementing treatment planning in RPT. This includes radiobiological modeling and microscale dosimetry calculations for alpha-particle emitter RPT. 2. Pre-clinical studies using novel alpha-emitter RPT agents with immune intact transgenic animal models that incorporate modeling and dosimetry to support the translation of novel targeted radionuclide therapy strategies to the clinic. In particular, identifying how to best combine RPT with complementary orthogonal-modality agents while also obtaining a basic understanding of how the treatment works and which variables have the greatest impact on efficacy and toxicity. The underlying objective is to utilize pre-clinical modeling and dosimetry to help identify an optimal therapeutic clinical trial design so as to reduce unnecessary human experimentation.

The Retinal Cell and Molecular Laboratory has three major areas of interest, each of which deals with some aspect of growth factor signaling and function in the retina and retinal pigmented epithelium (RPE): 1. Investigations aimed at gaining a better understanding of the pathogenesis of retinal and choroidal neovascularization and developing new ways to treat them. 2. Investigations aimed at understanding the molecular signals involved in retinal and RPE wound repair and scarring. The prototypical disease in this category is proliferative vitreoretinopathy and our laboratory is seeking to identify new treatments for it. 3. Investigations aimed at understanding why retinal degenerations occur and how they might be treated, with particular emphasis on neurotrophic factors.

Epstein-Barr virus and Kaposi's sarcoma herpesvirus are found in association with a variety of cancers. Our laboratory studies are aimed at better defining the role(s) of the virus in the pathogenesis of these diseases and the development of strategies to prevent, diagnose or treat them. We have become particularly interested in the unfolded protein response in activation of latent viral infection. Among the notions that we are exploring is the possibility that activation of virus-encoded enzymes will allow the targeted delivery of radation. In addition, we are investigating a variety of virus-related biomarkers including viral DNA, antibody responses, and cytokine measurements that may be clinically relevant.

Research in the Robert Siliciano Laboratory focuses on HIV and antiretroviral therapy (ART). ART consists of combinations of three drugs that inhibit specific steps in the virus life cycle. Though linked to reduced morbidity and mortality rates, ART is not curative. Through our research related to latently infected cells, we've shown that eradicating HIV-1 infection with ART alone is impossible due to the latent reservoir for HIV-1 in resting CD4+ T cells. Our laboratory characterized the different forms of HIV-1 that persist in patients on ART. Currently, we are searching for and evaluating drugs that target the latent reservoir. We are also developing assays that can be used to monitor the elimination of this reservoir. We are also interested in the basic pharmacodynamic principles that explain how antiretroviral drugs work. We have recently discovered why certain classes of antiretroviral drugs are so effective at inhibiting viral replication. We are using this discovery along with experimental and computational approaches to develop improved therapies for HIV-1 infection and to understand and prevent drug resistance. Finally, we are studying the immunology of HIV-1 infection, and in particular, the ability of some patients to control the infection without ART.

Investigators in the Robert Brodsky Lab study normal and abnormal hematopoiesis, particularly mutations of the phosphatidylinositol glycan anchor biosynthesis class A (PIG-A) gene in aplastic anemia. Our team has developed a new diagnostic assay for paroxysmal nocturnal hemoglobinuria (PNH) that is based on the toxin Aaeromonas hydrophila.

Reid Thompson’s research interests include evaluation of ventricular function in patients with muscular dystrophy and Barth syndrome, and in patients who have completed chemotherapy. He also studies novel methods of teaching and diagnosing heart disease through cardiac auscultation.

Research in the Howard and Georgeanna Seegar Jones Reproductive Endocrinology Lab supports a broad interest in reproductive conditions, but has a particular focus on endometriosis, uterine fibroids, polycystic ovary syndrome (PCOS) and genes causing infertility. PCOS and uterine fibroids are among the most prevalent conditions leading to infertility and diseases in women, but both remain poorly understood. Studying these areas may lead to the development of new treatments or preventative therapies.